The tooth is an organ, which can be lost by dental caries, periodontal diseases or the like, and which has hard tissues such as enamel in the outermost layer and dentin in the inner layer, and further has an odontoblast which forms dentin in the deeper layer of the tooth and dental pulp in the core. Generally, tooth loss today is mainly compensated for by dentures and implants in many cases, as this is thought to have little threat to life. However, there is a growing interest in the development of tooth regenerative technology in view of the significant influence that the presence or absence of teeth has on personal appearance and on the taste of food, and from the perspective of maintaining health and a high quality of life.
Teeth are functional units that are formed by induction during the developmental process of the fetal stage and constructed with plural cell types, and they are thought to be the same as organs or internal organs. Therefore, teeth are not produced by the stem cell system in which cell types are produced from stem cells such as hematopoietic stem cells and mesenchymal stem cells in the adult body, and teeth cannot be regenerated solely by stem cell implantation (stem cell implant therapy) which is currently under development by regenerative medicine. Moreover, while regeneration of teeth by identifying the gene that is specifically expressed in the tooth developmental process and artificially inducing a tooth germ is being considered, tooth regeneration cannot be induced completely simply by identifying the gene.
Therefore, studies have been conducted recently with a central focus on tooth regeneration by transplanting a reconstituted tooth germ obtained by reconstituting a tooth germ using isolated tooth germ cells.
For example, in Non-patent Document 1, it is disclosed that a tooth-like tissue is regenerated by transplanting cells, such as epithelial cells isolated from a tooth germ and mesenchymal dental follicle cells, with a bioabsorbable carrier into an abdominal cavity of a rat.
In Non-patent Document 2, it is described that co-culture by collagen gel is effective as a system in which an epithelium/mesenchymal interaction by subcultured cells can be realized.
As a method of regenerating a tooth germ, it is described, for example, in Patent Document 1, that tooth germ cells are cultured in the presence of physiologically active substances such as fibroblast growth factors and the like. In Patent Document 2, it is proposed that at least one type of cells selected from tooth germ cells and cells which can be differentiated into these tooth germ cells are cultured along with a fibrin-containing carrier, and it is described that a “tooth” having a specific shape is formed by using a fibrin-containing carrier having the desired shape for the tooth germ.
In Patent Documents 3 and 4, a method of forming teeth is disclosed that includes seeding a cell mixture of a tooth germ containing dentin forming mesenchymal cells derived from dental pulp and epithelial cells which contribute to enamel formation, from the mandible of a 6 month-old pig, into a scaffold which is a solidified biodegradable polymer containing a polyglycolic acid/polyacetic acid copolymer; and transplanting it into an animal body. Here, it is described that a “tooth” having a specific shape is formed by using a scaffoldhaving the desired shape for the tooth germ.
Further, in Patent Document 5, a method of tooth regeneration for treating a patient with bone loss or damage is disclosed. According to this method, a bone is formed by seeding mesenchymal cells in a polyglycolic acid mesh carrier and then laminating the carrier with epithelial cells and collagen or wrapping it with an epithelial cell sheet. Further, in Patent Document 5, a carrier is used to construct the shape of a bone.
Non-patent Document 1: J. Dent. Res., 2002, Vol. 81 (10), pp. 695-700
Non-patent Document 2: “Regenerative medicine using teeth and cells derived from a tooth germ and the possibility of the same,” Regenerative Medicine, Journal of the Japanese Society for Regenerative Medicine, 2005, Vol. 4(1), pp. 79-83
Patent Document 1: Japanese Patent Application Laid-open No. 2004-331557
Patent Document 2: Japanese Patent Application Laid-open No. 2004-357567
Patent Document 3: US Patent Application Publication No. 2002/0119180
Patent Document 4: US Patent Application Publication No. 2004/0219489
Patent Document 5: International Publication (WO) No. 2005/014070